Role of stem cell therapies in treating chronic wounds: A systematic review

Abstract

BACKGROUND The impairment of cutaneous wound healing results in chronic, non-healing wounds that are caused by altered wound environment oxygenation, tissue injury, and permissive microbial growth. Current modalities for the treatment of these wounds inadequately address the complex changes involved in chronic wound pathogenesis. Consequently, stem cell therapies have emerged as a potential therapeutic modality to promote cutaneous regeneration through trophic and paracrine activity. AIM To investigate current literature regarding use of stem cell therapies for the clinical treatment of chronic, non-healing wounds. METHODS PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus were queried with combinations of the search terms “mesenchymal stem cells,” “adult stem cells,” “embryonic stem cells,” “erythroid precursor cells,” “stem cell therapies,” and “chronic wounds” in order to find relevant articles published between the years of 2000 and 2019 to review a 20-year experience. Reference lists from the articles were reviewed to identify additional pertinent articles. Retrieved manuscripts (reviews, case reports/series, retrospective/prospective studies, and clinical trials) were evaluated by the authors for their depiction of clinical stem cell therapy use. Data were extracted from the articles using a standardized collection tool. RESULTS A total of 43 articles describing the use of stem cell therapies for the treatment of chronic wounds were included in this review. While stem cell therapies have been explored in in vitro and in vivo applications in the past, recent efforts are geared towards assessing their clinical role. A review of the literature revealed that adipose-derived stem cells, bone marrow-derived stem cells, bone marrow-derived mononuclear cells, epidermally-derived mesenchymal stem cells, fibroblast stem cells, keratinocyte stem cells, placental mesenchymal stem cells, and umbilical cord mesenchymal stem cells have all been employed in the treatment of chronic wounds of various etiologies. Most recently, embryonic stem cells have emerged as a novel stem cell therapy with the capacity for multifaceted germ cell layer differentiation. With the capacity for self-renewal and differentiation, stem cells can enrich existing cell populations in chronic wounds in order to overcome barriers impeding the progression of wound healing. Further, stem cell therapies can be utilized to augment cell engraftment, signaling and activity, and resultant patient outcomes. CONCLUSION Assessing observed clinical outcomes, potential for stem cell use, and relevant therapeutic challenges allows wound care stakeholders to make informed decisions regarding optimal treatment approaches for their patients’ chronic wounds.

Biofilm-Innate Immune Interface: Contribution to Chronic Wound Formation

“…Moreover, addition of hASCs in comparison to hydrogel treatment alone increased the M2/M1 macrophage ratio, suggesting that hASCs can promote the transition to the repair phase of healing (252). A recent systematic review by Raghuram et al, identified adipose-derived stem cells, bone marrow-derived stem cells, bone marrow-derived mononuclear cells, epidermally derived mesenchymal stem cells, fibroblast stem cells, keratinocyte stem cells, placental mesenchymal stem cells, and umbilical cord mesenchymal stem cells being used in vitro and in vivo as potential treatments for chronic wounds, however, clinical effectiveness still requires investigation due to heterogeneity of wound etiology (253).…”

Synergistic Effect of Biomaterial and Stem Cell for Skin Tissue Engineering in Cutaneous Wound Healing: A Concise Review

“…The study further states that exosomes derived from human ESCs can behave like their parental ESCs and contribute to antiaging and regenerative medicine via transfer and encapsulation of bioactive molecules to target cells. Although in vivo study of ESCs shows promising results in wound healing, its clinical use is limited by the ethical controversy revolving their procurement process as it can induce damage to the human embryo [ 62 ]. Instead, much interest is being developed towards ASCs and iPSCs as they possess minimal ethical concerns relating to procurement and clinical translation.…”

“…Apart from MSCs and ASCs, bone marrow-derived stem cells (BM-SCs), and human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are good candidates for the treatment of different types of wounds [ 11 ]. hUC-MSC isolated from umbilical cord lining tissue represents another mesenchymal stem cell population [ 62 ]. Notably, the epithelial cells belonging to the umbilical cord possess stem cell-like properties and can differentiate into any form of stratified epithelium required for improved wound healing [ 56 ].…”

Surgical and Nonsurgical Management of the Nasal Skin-Soft Tissue Envelope

“…15,42 Fatty tissue, for instance, harbors the potential to differentiate and to regenerate as it contains adipose derived stem cells. 43 These abilities have been used to treat and rehabilitate scars from burns and irradiation elsewhere in the body. [43][44][45] Remodeling of contracted atrophic soft tissue scars using autologous fat transfer in rhinoplasty has been described.…”

“…43 These abilities have been used to treat and rehabilitate scars from burns and irradiation elsewhere in the body. [43][44][45] Remodeling of contracted atrophic soft tissue scars using autologous fat transfer in rhinoplasty has been described. 42 The autologous fat transfer can be either injected preoperatively or intraoperatively using the microfat-infused soft tissue augmentation (MISTA) technique as described by Toriumi.…”